The objective of this project is to elucidate the relationship between molecular composition and topographic arrangements of membrane building blocks with reference to plasma membrane function. Bioelectrogenesis, transport and many metabolic phenomena are based on the proper associations of membrane proteins and lipids. Membrane ecto-enzymes are glycoproteins and require a lipophilic environment for optimal activity. Ecto-phosphoesterhydrolases appear to be a part of a regulatory system which modulates membrane permeability and excitability. We have challenged this system by inactivation of ecto-5-nucleotidase with membrane impermeable modifiers such as Conconavalin A or trinitrobenzenesulfonic acid. Cultured brain cells respond by replacing the surface enzyme and decreasing exfoliation of activity in the form of microvesicles (exosomes). This response appears to be the result of recognition of decreased ecto-5'-nucleotidase activity and selective conservation of the enzyme in the exfoliative process. Studies of ATPases in human erythrocyte membranes of normal and manic-depressive populations suggest that the variations found in patients with bipolar effective disorders is caused by periodic fluctuations in levels of factor(s) which bind to erythrocyte membranes and radically alter their biological properties.